Process for the prepartion of 1,3,5-tris(4&#39;-hydroxyaryl)benzene

ABSTRACT

Novel 4-substituted acetophenone anils and methods for preparing 1,3,5-tris(4&#39;-hydroxyphenyl)benzenes from 4-substituted acetophenones such as 4-hydroxyacetophenones or, from substituted 4-hydroxyacetophenone-anils such as 4-hydroxyacetophenone-anil by reacting the 4-substituted acetophenone or corresponding anil with an aniline derivative.

CROSS REFERENCE TO RELATED APPLICATIONS

Reference is hereby made to the commonly owned and concurrently filedapplication of Aslam et al. entitled Process for the Preparation of1,3,5-tris(4'-hydroxyphenyl)benzene and its Derivatives and IntermediateCompounds Serial No.07/891,167, filed Jan. 08, 1992, and the applicationof Hilton entitled Epoxidation Products of1,3,5-(4'-hydroxyphenyl)benzenes, Ser. No. 07/819,166, filed Jan. 08,1992.

FIELD OF THE INVENTION

This invention relates to a process for preparing1,3,5-tris(4'-hydroxyphenyl)benzene (THPB) and related compounds from4-hydroxyacetophenones (4-HAP). Condensation of three acetophenonemolecules produces an aromatic nucleus to provide 1,3,5-trisphenylbenzenes.

BACKGROUND OF THE INVENTION

1,3,5-tris(4'-hydroxyphenyl)benzene falls into the class of compoundsknown as trisphenyls. Trisphenyls have been recognized as usefulintermediates in the preparation of more complex organic structures. Forexample, resins are readily prepared by a reacting trisphenyls withformaldehyde, acid anhydrides and more importantly with epichlorohydrin.Epoxide resins prepared from such compounds exhibit low shrinkage,extraordinary hardness, chemical inertness, outstanding mechanicalstrength, and a variety of beneficial features. See, for example, U.S.Pat. No. 4,394,496; and, the above-referenced application of Hilton.

1,3,5-tris(4'-hydroxyphenyl)benzene (THPB) molecules are particularlyuseful in their ability to stabilize polycarbonates. This isaccomplished via a three site rigid D_(3h) crosslink. THPB molecules mayalso be used as crosslinking agents in epoxy resins. See, for example,Chem. Abstracts., 66, 3004C.

THPB was reported in Beilstein, E II 6, 1115 (1921). The treatment of4-methoxyacetophenone (4-MAP) with sulfuric acid produced1,3,5-tris(4'-methoxyphenyl)benzene (4-MAP trimer or TMPB)(20% yield).This compound was demethylated with concentrated hydrochloric acid toyield THPB.

THPB was also reported in Chimia, 12, 143 (1958) and in Chimia, 13, 105(1959) as formed by the trimerization of 4-haloacetophenone, where thehalogen is either bromine or chlorine, in the presence of potassiumpyrosulfate and sulfuric acid. This reaction results in1,3,5-tris(4'-halophenyl)benzenes. These halogen-containing trimers weretreated with sodium hydroxide and converted to THPB.

M. H. Karger and Y. Mazur, J. Org, Chem, 36, 540 (1971), reported thatanisole and acetyl methanesulfonate, affords 4-MAP (46% yield) and TMPB(41% yield). Subsequent to anisole acetylation, trimerization iscatalyzed by methanesulfonic acid.

R. E. Lyle, E. J. DeWitt, N. M. Nichols, and W. Cleland, J. Amer. Chem.Soc., 75, 5959 (1953), report the trimerization of substitutedacetophenones, i.e., 4-MAP to TMPB (54% yield), by an alcoholic hydrogenchloride solution, after four months at room temperature.

G. P. Sharnin, I. E. Moisak, E. E. Gryazin, Zhurnal Prikladnoi Khimii,43, 1642 (1970), report the trimerization of 4-MAP to TMPB (27% yield)using a mixture of potassium pyrosulfate and sulfuric acid. See also, A.F. Odel et al., J. Amer, Chem, Soc., 36, 81 (1913).

P. Milart and J. Cioslowski, Synthesis, p. 328-29 (1984) relate to theuse of 4-alkoxyacetophenones to prepare 4-alkoxyacetophenone anils whichare condensed to form 1,3,5-tris(4'-alkoxyphenyl)benzenes. However, thereference does not suggest using 4-hydroxyacetophenone (4-HAP) orsubstituted 4-hydroxyacetophenones to produce 4-hydroxyacetophenone-anil(4-HAP-anil) or substituted 4-hydroxyacetophenone-anils, which may bethen condensed to form 1,3,5-tris(4'-hydroxyphenyl)benzene orsubstituted 1,3,5-tris(4'-hydroxyphenyl)benzenes. In fact, the referenceteaches the conversion of 4-hydroxyacetophenone to 4-alkoxyacetophenonebefore converting to the corresponding anil and thereafter trimerizingthe anil. This is consistent with earlier teachings which describeunsuccessful efforts to trimerize hydroxyacetophenone. See, for example,G. P. Sharnin et al., supra, see also R. E. Lyle et al., supra. Its isalso consistent with prior teachings that1,3,5-tris(4'-hydroxyphenyl)benzene is produced by hydrolyzing thecorresponding 4'-alkoxy substituted compound which is prepared using4-alkoxyacetophenone. See, for example, Beilstein, E II 6, 1115 (1921).Moreover, P. Milart et al. fail to teach or suggest a one step processfor trimerizing 4-HAP.

U.S. Pat. No. 3,458,473, issued Jul. 29, 1969 to Starnes et al. isdirected to the preparation of various hindered trisphenyls prepared bythe cyclotrimerization of an acetylphenol precursor.

U.S. Pat. No. 3,644,538 issued Feb. 22, 1972 to W. H. Starnes, disclosesthat both 3'-alkyl- and 3',5'-dialkyl-4'-hydroxyacetophenones can betrimerized to the corresponding triarylbenzenes with anhydrous HCl andtriethyl orthoformate and ethanol. Trimerization of unsubstituted 4-HAPis not suggested or disclosed. Starnes also fails to teach or suggesttrimerizing substituted or unsubstituted 4-HAP-anil.

German Patent 258,929 to Zimmerman et al., issued Aug. 10, 1988 isdirected to methods for the production of 1,3,5-tris(triarylbenzene)compounds. These compounds are reacted by combining 2,4,6-triarylpyrylium salts with carboxylic acid anhydride in the presence of a basiccondensing agent. The reaction of Zimmerman utilizes triaryl pyryliumcarboxylic anhydride.

Elmorsy et al., "The Direct Production of Tri- and Hexa-SubstitutedBenzenes from Ketones Under Mild Conditions," Tetrahedron Letters, Vol.32, No. 33, pp. 4175-4176 (1991) report the treatment of aryl benzeneswith tetrachlorosilane in ethanol to yield 1,3,5-triarylbenzenes.However, Elmorsy et al. fail to teach or suggest trimerizing4-hydroxyacetophenone, a 4-hydroxyacetophenone derivative, or a4-substituted-oxyacetophenone by contacting such a compound with ahalosilane, as in the present invention. Indeed, it is believed thattrimerizing a hydroxyacetophenone such as 4-hydroxyacetophenone or a4-hydroxyacetophenone derivative, is not disclosed or suggested byElmorsy et al. because of the belief that the hydroxy group wouldinterfere with the reaction, for example, react with thetetrachlorosilane. See, e.g,, Sharin et al., supra, which illustrate whyit was believed, before now, that direct trimerization ofhydroxyacetophenone was not feasible. Accordingly, Elmorsy et al. failto teach or suggest the present invention.

SUMMARY OF THE INVENTION

In accordance with this invention, a process is provided for thepreparation of 1,3,5-tris(4'-hydroxyphenyl)benzene (THPB) and relatedcompounds from 4-hydroxyacetophenone (4-HAP) and correspondingsubstituted 4-hydroxyacetophenones. Until now, the direct trimerizationof 4-hydroxyacetophenone (4-HAP) to 1,3,5-tris(4'-hydroxyphenyl)benzene(THPB) was believed to be not feasible.

The inventive reaction provides a novel approach for the large scalesynthesis of 1,3,5-tris(4'-hydroxyphenyl)benzene or related compounds.In a broad sense, the present invention provides a process for theproduction of 1,3,5-tris(4'-hydroxyphenyl)benzene or its relatedcompounds by contacting the corresponding substituted4-hydroxyacetophenone with aniline or an aniline derivative to form the4-hydroxyacetophenone-anil, and, contacting the4-hydroxyacetophenone-anil with a catalytic amount of an acid catalyst,preferably an anilinium salt, such as anilinium hydrochloride, aniliniumhydrobromide, anilinium sulfate, anilinium tosylate and the like, toform 1,3,5-tris(4'-hydroxyphenyl)benzene or its related compounds. Theterm "aniline derivative" refers to substituted aniline wherein thesubstituents are on the aromatic ring of the aniline and are selectedfrom the group consisting of C₁ -C₆ alkyl, C₁ -C₆ alkoxy, and halo. Thescope of the invention also provides for the use of naphthylamine andnaphthylamine derivative in place of aniline and aniline derivativerespectively, and of naphthylaminium salt in place of the aniliniumsalt, as is known to those skilled in the art.

More specifically, the process comprises treating 4-hydroxyacetophenoneor other substituted 4-hydroxyacetophenones with aniline, preferably byrefluxing, and preferably in the presence of a solvent such as tolueneto produce 4-hydroxyacetophenone-anil (4-HAP-anil) or the correspondingsubstituted 4-hydroxyacetophenone-anil. The 4-hydroxyacetophenone-anilor substituted 4-hydroxyacetophenone-anil is trimerized in the presenceof an acid catalyst, e.g., HCl, HBr, H₂ SO₄ or the like, preferably anacidic anilinium salt such as anilinium hydrochloride, aniliniumhydrobromide, anilinium sulfate or anilinium tosylate to produce1,3,5-tris(4'-hydroxyphenyl)benzene or the corresponding substituted1,3,5-tris(4'-hydroxyphenyl)benzene. The present invention also providesa process for the production of 1,3,5-tris(4'-hydroxyphenyl) benzenecomprising contacting 4- hydroxyacetophenone-anil with aniliniumhydrochloride, under reaction conditions.

The inventive process is based on the following general reaction inwhich three acetophenone molecules, e.g., 4-hydroxyacetophenone orsubstituted 4-hydroxyacetophenone molecules, are condensed to provide a1,3,5-tris(4'-hydroxyphenyl)benzene or substituted1,3,5-tris(4'-hydroxyphenyl)benzene. ##STR1##

In one embodiment, the reaction can be carried out in one step, withoutthe isolation of 4-hydroxyacetophenone-anil or a substituted4-hydroxyacetophenone-anil. In the reaction, the 4-hydroxyacetophenoneor a substituted 4-hydroxyacetophenone is treated with the aniline inthe presence of an acid catalyst to form the1,3,5-tris(4'-hydroxyphenyl)benzene or a substituted1,3,5-tris(4'-hydroxyphenyl)benzene. ##STR2##

In each of the above reaction schemes, R¹ is hydrogen, an alkyl groupsuch as an alkyl group having from I to about 12 carbon atoms preferablya C₁ -C₅ lower alkyl, such as methyl or ethyl, a cycloalkyl of fromabout 3 to about 6 carbon atoms, phenyl (including mono orpolysubstituted phenyl, e.g., with halogen and/or nitro) , halogen, suchas Br, Cl, I or F, NO₂ or sulf onyl (alkyl or aromatic). The alkyl groupof the alkyl sulfonyl is preferably an alkyl group having from I toabout 12 carbon atoms, more preferably a C₁ -C₅ lower alkyl, forinstance, a C₁ -C₅ lower alkyl substituted by one or more halogen and/ornitro groups. The aromatic of the aromatic sulfonyl is preferablyphenyl, or an alkyl substituted aromatic such as an aromatic substitutedby one or more lower alkyl groups, for instance, tolyl, xylyl, cumenylor the like, or an aromatic substituted by one or more halogen and/ornitro groups.

In addition, the acetophenone molecule can have from one to four R¹substituents on it (e.g., at any or all of the 2, 3, 5 and 6 positions);and, these multiple R¹ substituents can be the same or different. Thus,x can be an integer from 1 to 4, and, when x is greater than 1, the R¹substituents can be the same or different.

In the inventive process, it has been found, surprisingly, that the4-hydroxyacetophenone carbonyl group is converted to the aniline imine,which undergoes cyclotrimerization readily in the presence of theacidic, preferably anilinium salt, condensing agent which is regeneratedin the process.

A significant advantage of the process of the invention is that theprocess may be carried out in a single step and provides for theproduction of THPB and its derivatives, without using a number ofreaction steps and reagents which were necessary in the past.

DETAILED DESCRIPTION

An embodiment of the present invention is exemplified by the followinggeneral reaction in which three acetophenone molecules are condensed toprovide a 1,3,5-trisaryl benzene: ##STR3##

Another embodiment of the present invention is illustrated by thepreparation of THPB from 4-HAP by the following reaction scheme:##STR4##

Yet another embodiment of the present invention is illustrated by thefollowing one step process to prepare THPB from 4-HAP. ##STR5##

In this one step process, the 1,3,5-trisaryl benzene such as THPB isprepared, via a conversion from the corresponding substituted4-hydroxyacetophenone such as 4-HAP without the isolation of the4-hydroxyacetophenone-anil such as 4-HAP-anil. Generally, threeacetophenone molecules, in the presence of sufficient quantities ofaniline and anilinium hydrochloride, and optionally in the presence of asolvent, for example, a non-polar solvent such as toluene, are condensedto provide the corresponding 1,3,5-trisaryl benzene. Reaction conditionscan be varied but generally are ambient pressure and temperatures andtimes which do not significantly decompose the reactants and/or product,and, which provide a satisfactory yield of desired product. Typicalreaction times are about 0.5 to 8 hours, and typical reactiontemperatures range from about 500° to about 2200C.

Alternatively, the substituted 4-HAP can be contacted with an aniline toyield the anil; the contacting is preferably in the presence of asolvent. Anilinium hydrochloride is thereafter added in a sufficientquantity and the solvent removed by distillation. These reactionmixtures are each heated at a temperature and for a time, again, so asto not result in significant decomposition of reactants and/or product,and, so as to obtain a satisfactory yield of desired product. Forcontacting the substituted 4-HAP with an aniline derivative to yield theanil, the reaction conditions are typically times of 2 to 24 hours andtemperatures of 800° to 160° C.; and, for contacting the anil with theacidic anilinium salt (e.g., anilinium hydrochloride), the reactionconditions are typically times of 0.25 to 4 hours and temperatures of1800 to 2200° C.

The 1,3,5-trisaryl benzene, for instance, THPB, is recovered from thereaction mixture by, for instance, cooling the reaction mixture andprecipitating the product; addition of a suitable solvent, for example,a non-polar solvent such as toluene, in a suitable amount, to separateout oil, decanting the supernatant liquid to leave an oily residue, andadding a suitable solvent, for example, a non-polar solvent such ashexane, to the oily residue to cause the THPB to precipitate is alsopossible. The 1,3,5-trisaryl benzene such as THPB is preferablyrecrystallized to increase its purity. Whether the 1,3,5-trisarylbenzeneis prepared from corresponding acetophenone or acetophenone-anil asillustrated above, the starting material is to be used in at least 3molar ratios with respect to the quantity of the end product.

It is within the ambit of the skilled artisan to select appropriatequantities of the reactants, aniline, anilinium salts and solvent and toselect appropriate reaction times and temperatures. The selection ofappropriate reaction times and temperatures depends upon variousfactors, such as the quantity of reactants. Furthermore, in thisDescription, wherever aniline is described as a reactant, it is to bepresumed that aniline derivative, as explained above, may be substitutedas a reactant.

When the aniline and anilinium salt are aniline and aniliniumhydrochloride respectively, it is preferred that the number of moles ofaniline present during the reaction be at least equal to or more thanthe number of moles of the substituted 4-hydroxyacetophenone present.The ratio of the number of moles of aniline to the number of moles ofthe substituted 4-hydroxyacetophenone (e.g., aniline:4-hydroxyacetophenone) is about 1.0:1.0 to about 10:1. The aniline:substituted 4-hydroxyacetophenone mole ratio is most preferably about2:1.

Anilinium hydrochloride is present in sufficient quantities to catalyzethe cyclotrimerization and the regeneration of aniline. In the reactionmixture, the ratio of the number of moles of anilinium hydrochloride tothe number of moles of the 4-hydroxyacetophenone such as 4-HAP ispreferably about 0.01:1 to about 0.25:1 (or about 1:4 to about 1:100).

When the aniline: 4-hydroxyacetophenone mole ratio is about 2:1, theratio of the number of moles of anilinium hydrochloride to the number ofmoles of 4-hydroxyacetophenone is about 0.02:1 to about 0.1:1,preferably about 0.04:1.0 (or, about 1.0:10 to about 1.0:50, preferablyabout 1.0:25). Likewise, a preferred ratio of the number of moles ofaniline initially added to the number of moles of aniliniumhydrochloride is about 1:0.02, when the aniline: 4-hydroxyacetophenonemole ratio is about 2:1.

As to the solvents used in the reaction, the substituted4-hydroxyacetophenone and aniline are preferably contacted in thepresence of a solvent such as toluene. A preferred solvent to add to thecooled reaction mixture is also toluene, and, it is preferably added inabout the same amount used during the initial contacting. To precipitatethe 1,3,5-tris(4'-hydroxyaryl)benzene from the oily residue, hexane is apreferred non-polar solvent, and, it is preferably present in excess.

Other suitable solvents used during the reaction of the4-hydroxyacetophenone in the presence of the aniline include xylene;during the oil separation include pentane; and, during the precipitationof the 1,3,5-tris(4-hydroxyaryl)benzene may be pentane, cyclohexane, andthe like.

The aniline and aniline derivatives utilized to promote the formation ofthe 4-hydroxyacetophenone-anil are aniline, p-methyl aniline, nitroaniline, chloro aniline, and the like. Acids such as HCl, HBr, H₂ SO₄and the like may be used to catalyze the condensation to the1,3,5-tris(4'-hydroxyaryl)benzene; however, acids derived from aniline,especially from the aniline used to form the anil, are preferred.Suitable acidic anilinium salts include aniline•HCl, aniline•HBr,aniline•sulfate, aniline•tosylate, or the like.

In another embodiment, the 4-hydroxyacetophenone-anil is prepared,isolated and then utilized to form the corresponding 1,3,5-trisarylbenzene. According to this process, in an initial reaction, a suitablequantity of the 4-hydroxyacetophenone such as 4-HAP is contacted withaniline, optionally in the presence of a solvent, e.g., a non-polarsolvent such as toluene, under reaction conditions, to form thecorresponding anil compound. The reaction conditions are temperature,time and pressure conditions which do not cause significantdecomposition of reactants and/or product, and, which obtain asatisfactory yield of desired product. Typical reaction conditionsinclude temperatures of about 1500° C. to about 180° C. times of about 2to about 24 hours and pressures of about 50 mm to about 760 mm Hg. Forexample, the reaction may be carried out under reflux for up to 17 hoursat a pressure achieved using a condenser and Dean Stark trap. Conditionsmay vary depending upon the scale of the reaction (quantities ofreactants) and other factors usually considered by the skilled artisan.

The number of moles of aniline present is an amount at least equal to orpreferably exceeding the number of moles of the 4-hydroxyacetophenonepresent. The mole ratio of aniline: 4-hydroxyacetophenone ranges fromabout 1:1 to about 10:1, most preferably about 3.0:1.0. A preferredsolvent for this reaction is toluene. This invention is not limited tothe use of toluene as a solvent as other suitable solvents may also beemployed, including xylene, cyclohexane and the like.

As the 4-hydroxyacetophenone and aniline are reacted, water from thereaction is collected by, for example, a trap via a condenser, and,after a sufficient time, the 4-hydroxyacetophenone-anil is recoveredfrom the reaction mixture. For instance, when the reaction is complete,the reaction mixture is cooled after a period of time, for example, upto 17 hours and, then combined with a solvent, for example, a non-polarsolvent such as hexane, to form an oily product, e.g. a yellowish-brownoily product in the case of 4-hydroxyacetophenone-anil, which separatesout of the reaction mixture. The quantity of hexane used is preferablyabout 2.5 to about 500 moles per mole of the 4-hydroxyacetophenoneinitially added. Most preferably, the ratio is about 8.0:1.0. The oilyproduct is recrystallized with a solvent, for example, a non-polarsolvent such as hexane, to afford a solid. The recrystallization solventis preferably used in an amount of the order mentioned above for thesolvent utilized to separate the oily product from the cooled reactionmixture (e.g., on a small scale 3×200 ml). The solid is preferablyrecrystallized to afford a solid, e.g., 4-HAP-anil. Any suitable solventor solvent combination, e.g., non-polar solvents or combinations ofrelatively non-polar solvents may be employed for the recrystallization.Ether/hexane is one suggested solvent combination for therecrystallization. However, the invention is not limited to theserecovery steps for obtaining the anil compound from the reaction mixtureas other effective procedures or solvents may be used, such othersolvents including pentane, cyclohexane and the like.

4-Hydroxyacetophenone-anil compounds such as 4-HAP-anil may be reactivewith water and should be kept dry prior to their further use.

In a second step the 4-HAP-anil isolated from the first step iscontacted with an acid catalyst, preferably an anilinium salt such asanilinium hydrochloride under suitable reaction conditions to producethe desired 1,3,5-trisaryl benzene product. The mole ratio of aniliniumhydrochloride to substituted 4-hydroxyacetophenone-anil is preferablyabout 0.01:1 to about 0.25:1, more preferably about 0.065:1.0 (or,preferably about 1.0:4.0 to about 1.0:100, more preferably about 1:15).The mole ratios for the two-step process may also be in the rangesdescribed above in connection with the "one step" embodiment of thepresent invention, for instance ranges of about 1.0:4.0 to 1.0:100, andabout 1:10 to about 1:50 such as about 1:12.5 to about 1:25 for theanilinium hydrochloride to 4-hydroxyacetophenone-anil mole ratio.

The reaction conditions of this second step are suitable time andtemperature which will not cause significant decomposition of reactantsand/or product, and, will obtain a satisfactory yield of the desiredproduct. Reaction times of about 0.25 to about 4 hours and temperaturesof about 1800° to about 2200° C. are preferred, e.g., reflux (about1900° C.) for about 2 hours.

The reaction mixture is cooled and extracted into an aqueous solution,e.g., a basic aqueous solution such as an aqueous alkali hydroxidesolution, such as NaOH. When a NAOH solution is used, it may be used ina 1 molar solution (e.g., in small scale 2 g NAOH in 50 ml H₂ O).Extracting the reaction mixture into an aqueous solution results in asecond aqueous solution which is washed with an organic solvent, suchas, a relatively non-polar solvent like chloroform (e.g., two times, orin small scale 2×25 ml) and acidified at a pH of, for example, about 6.5to 3.5, preferably about 5.5 to 4.0, whereby the1,3,5-tris(4'-hydroxyaryl)benzene precipitates. The solid may be dried,e.g., in a vacuum oven for about 2 to 24 hours at a temperature of about80 to 120° C. These recovery procedures are not limiting as variationsare within the ambit of the skilled artisan. For instance, other aqueoussolutions including KOH, Na₂ CO₃ and the like, and, other organicsolvents such as methylene chloride and the like can be used.

Examples of 1,3,5-tris(4'-hydroxyaryl)benzenes which can be prepared inaccordance with the invention are:

1,3,5-tris(4'-hydroxyphenyl)benzene;

1,3,5-tris(3'-alkyl-4'-hydroxyphenyl)benzene;

1,3,5-tris(3'-halophenyl-4'-hydroxyphenyl)benzene;

1,3,5-tris(3'-nitro-4'-hydroxyphenyl)benzene;

1,3,5-tris(2'-alkyl-4'-hydroxyphenyl)benzene;

1,3,5-tris(2'-alkyl-3'-alkyl 4'-hydroxyphenyl)benzene;

1,3,5-tris(2'-nitro-3'nitro 4'-hydroxyphenyl)benzene; and

1,3,5-tris(2'-halophenyl-3'-halophenyl 4'-hydroxyphenyl)benzene andcombinations thereof, e.g.1,3,5-tris(2'-alkyl-6'-halo-4'-hydroxyphenyl)benzene.

Examples of 4-hydroxyacetophenones used in the reaction are:

4-hydroxyacetophenone;

3-alkyl-4-hydroxyacetophenone;

3-halo-4-hydroxyacetophenone;

3-nitro-4-hydroxyacetophenone;

2-alkyl-4-hydroxyacetophenone;

3-alkyl-4-haloacetophenone; and

2-alkyl-6-halo-4-hydroxyacetophenone.

From the above examples of 1,3,5-tris(4'-hydroxyaryl)benzenes which canbe prepared in accordance with the invention, and, the above examples of4-hydroxyacetophenones used in the reaction, it is to be understood thatin the foregoing description terms such as "4-hydroxyacetophenone" and"substituted 4-hydroxyacetophenone" and abbreviations thereof caninclude both 4-hydroxyacetophenone, i.e., when R¹ is hydrogen and x is1, and substituted 4-hydroxyacetophenones, e.g., when R¹ can be otherthan hydrogen and x is 1 to 4, or when x is greater than 1 and the R'substituents are the same or different and include at least onesubstituent other than hydrogen. Likewise, in the foregoing description,the terms "1,3,5-tris(4'-hydroxyphenyl)benzene" and "substituted1,3,5-tris(4'-hydroxyphenyl)benzene" include1,3,5-tris(4'-hydroxyphenyl)benzene, i.e., when R¹ is hydrogen and x is1 as well as substituted 1,3,5-tris(4'-hydroxyphenyl)benzene, e.g., whenR¹ is other than hydrogen and x is 1 to 4, or when x is greater than 1and the R¹ substituents are the same or different and include at leastone substituent other than hydrogen. And, in this description the terms"1,3,5-trisaryl benzene" and "1,3,5-tris(4'-hydroxyaryl)benzene" aremeant to include both 1,3,5-tris(4'-hydroxyphenyl)benzene andsubstituted 1,3,5-tris(4'-hydroxyphenyl)benzene.

The inventive method may be further illustrated by the followingexamples, many apparent variations of which are possible withoutdeparting from the spirit and scope thereof.

EXAMPLE 1 One Step Conversion of 4-hydroxyacetophenone to THPB

4-Hydroxyacetophenone (13.6 g, 0.1 mol) was contacted with aniline (18.6g, 0.2 mol) in the presence of toluene (100 ml; as solvent) and heatedto reflux in a round bottom flask equipped with a condenser and a Deanand Stark trap. After most of the 4-HAP was converted to 4-HAP-anil(conversion followed by gas chromatography), anilinium hydrochloride(0.5 g, 0.0038 mol) was added and the toluene was removed viadistillation. The reaction mixture was heated at 190°-200° C. for 3hours, cooled to 120° C. and THPB was recovered as follows. Toluene (100ml) was added to the cooled reaction mixture and an oil was separated.The supernatant liquid was decanted leaving an oily residue to which wasadded hexanes (100 ml) to precipitate THPB as a yellow solid (5.3 g).THPB was 88% pure by HPLC analysis.

EXAMPLE 2 Synthesis of THPB via intermediate formation of4-hydroxyacetophenone (4-HAP) anil Step One: Preparation of 4-HAP-anil

4-Hydroxyacetophenone (27.2 g, 0.2 mol), was contacted with aniline (50g, 0.54 mol) in the presence of toluene (50 ml) of and heated to refluxin a round bottom flask equipped with a condenser and a Dean and Starktrap. The water from this reaction was collected in the trap. After 17hours, this reaction mixture was cooled and the 4-HAP-anil was recoveredby pouring the cooled reaction mixture into 200 ml of hexanes. Ayellowish-brown oily product separated out of the reaction mixture. Theoily product was triturated with hexanes (3×200 ml) to afford 45.0 g ofa brown solid. Recrystallization of a small sample (5.0 g) withether/hexane afforded 1.2 g of a yellowish-white solid which by meltingpoint (139°-141° C.) and ¹ H and ¹³ C NMR spectra was determined to be4-hydroxyacetophenone-anil (4-HAP-anil).

Step Two: THPB from 4-HAP-anil

To a round bottom flask equipped with a magnetic stirrer and acondenser, 4-hydroxyacetophenone-anil (2.5 g, 0.0118 mol) and aniliniumhydrochloride (0.1 g, 0.00077 mol) was added. The reaction mixture washeated at reflux (bath temperature 190° C.) for 2 hours, and cooled.THPB was recovered by extracting the reaction mixture into an aqueous 1molar NAOH solution (2 g NAOH in 50 ml water). The resulting aqueoussolution containing extracted reaction mixture was washed withchloroform (2×25 ml) and the chloroform wash was discarded. The aqueouslayer was acidified to a pH of 4.0, and the product precipitated as ayellow solid. The solid was dried in a vacuum oven to provide 1.4 g of84% pure THPB (by HPLC analysis).

EXAMPLE 3 4-HAP to THPB: One Step

4-hydroxyacetophenone (13.6 g) was contacted with (18.6 g) aniline andaniline-HCl (0.5 g) and heated to 185°-190° C. for two hours. A samplewas removed from the reaction mixture and by LC analysis determined tobe 31% 4-HAP and 67.5% THPB. Heating at 185°-190° C. continued foranother two hours and thereafter a sample was removed from the reactionmixture. By LC analysis, the reaction mixture after four hours was 23%4-HAP and 75% THPB. 10 ml of toluene was then added to the reactionmixture and heating at 190°-200° C. was continued for about another 2hours. A sample was then analyzed by LC analysis and determined to be 6%4-HAP and 93% THPB.

Heating was continued until most of the aniline was distilled out. TheTHPB was recovered by pouring the reaction mixture after the anilinedistillate was distilled out into dilute H₂ SO₄ and extracting withethyl acetate. The ethyl acetate was washed with water and product wascrystallized to yield (by LC analysis) 95% 4-HAP-trimer (THPB).

This Example demonstrates that the use of toluene solvent is optional,but preferred.

EXAMPLE 4 4-HAP to THPB: One Step

A reaction mixture of 4-hydroxyacetophenone (13.6 g), aniline (28.0 g)and aniline HCl (1.0 g) was heated to 220° C. in a reaction flask fittedwith a Dean and Stark trap filled with 90% aniline and stirred for 4hours at that temperature. The reaction mixture was cooled to roomtemperature and the THPB was recovered by pouring the cooled reactionmixture into a dilute sodium hydroxide solution (12.0 g NAOH in 200 mlH₂ O), separating out the aniline and washing the aqueous solution withchloroform. The aqueous layer was acidified, with drops of dilute HCl,to a pH of about 5.5, and a solid was precipitated. The precipitatedsolid was collected via filtration and dried in a vacuum oven to yield10.8 g. Using ¹ H and ¹³ CNMR and LC analyses, the product was 48% pure.Recrystallization would produce a more purified product.

EXAMPLE 5 4-HAP to 4-HAP-anil

A reaction mixture of 4-hydroxyacetophenone (27.2 g) and aniline (50.0g) in toluene (100 ml.) as solvent was mixed in a two-necked 500 mlflask equipped with a Dean and Stark trap and a condenser and heated toreflux using an oil bath at about 180° C. for 16 hours. Samples werewithdrawn at 4, 12, and 16 hours and analyzed by Gas Chromatography.After 4 hours there was 50% conversion to 4-HAP-anil; after 12 hoursthere was 80% conversion to 4-HAP-anil; and, after 16 hours there was88% conversion to 4-HAP-anil. After 16 hours, the reaction mixture wascooled, petroleum ether was added and an oily layer separated in thebottom. The oily layer was triturated with petroleum ether to give athick pasty oil which was dissolved in chloroform. The addition ofpetroleum ether resulted in a reddish brown solid. Gas Chromatography ona sample of this solid showed it to be 80% imine (4 -HAP-anil), 6%4-HAP, and 4.5% aniline. 5.0 grams of the solid was recrystallized withchloroform/hexane to give a yellow solid which was 96% pure 4-HAP-anilby Gas Chromatographic analysis. It was also observed that the4-HAP-anil was reactive with water. A sample of 4-HAP-anil left in anopen flask overnight hydrolyzed to 4-HAP and aniline as determined byGas Chromatography. Thus, the imine was kept dry prior to its use inmaking THPB.

EXAMPLE 6 THPB from 4-HAP-anil

In a flask, 4-hydroxyacetophenone-aniline imine (4-HAP-anil) (2.11 g;0.01 mol) was heated at about 1900C for 0.5 hours in the presence ofabout 0.1 g anilinium hydrochloride. The flask was cooled and theproduct was dissolved in dilute aqueous sodium hydroxide, and theaqueous solution was washed with chloroform. The aqueous layer wasseparated and acidified slowly by the addition of dilute HCl untilobtaining a pH of about 4.0. A yellow solid precipitated which wascollected via filtration, air dried and then dried in an oven at about70° C. and a pressure of about 50 mm Hg. The resultant solid weighed1.18 g and, by analysis, was 71.4% THPB and 0.6% 4-HAP.

EXAMPLE 7 THPB from 4-H&P-anil

Step two of Example 2 was repeated, except that the reaction mixture wasrefluxed for 4 hours. THPB was recovered as set out in step two ofExample 2 to provide 1.4 g of 75% pure THPB (by ¹³ C and ¹ H NMR andHPLC analyses).

Having described in detail preferred embodiments of the presentinvention, it is to be understood that the invention defined by theclaims is not to be limited by particular details set forth in thedescription as many apparent variations are possible without departingfrom the spirit of the present invention.

What is claimed is:
 1. A process for preparing a1,3,5-tris(4'-hydroxyaryl)benzene compound of formula (I): ##STR6##wherein R is hydroxy, R¹ is hydrogen, C₁ -C₁₂ alkyl, C₃ -C₆ cycloalkyl,phenyl, halogen, nitro, or alkyl or aromatic sulfonyl, x is an integerfrom 1 to 4, and when x is greater than 1 each R¹ thereof can be thesame or different, said process comprising reacting a substituted4-hydroxyacetophenone-anil compound of formula (III): ##STR7## whereinR, R¹ and x are as defined above, with an acid catalyst at about150°-220° C. for about 0.25 to about 4 hours with water beingcontinuously removed from the reaction, wherein compound III is presentin at least three molar ratio quantities and is kept substantiallyanhydrous prior to said reaction, wherein said acid catalyst is presentin a molar ratio range of about 1:4 to about 1:100 with respect tocompound III, and wherein said catalyst is a salt of aniline ornaphthylamine with said aniline or naphthylamine being substituted orunsubstituted in its aromatic ring, said substituents being selectedfrom the group consisting of a C₁ -C₆ alkyl, C₁ -C₆ alkoxy and halogroups.
 2. The process of claim 1 wherein the acid catalyst is aniliniumhydrochloride.
 3. The process of claim 1 wherein x is 1 and R¹ ishydrogen.
 4. The process of claim 2 wherein x is 1 and R¹ is hydrogen.5. The process of claim 4 wherein the mole ratio of aniliniumhydrochloride compound of formula (III) is about 1.0:12.5 to about1.0:25.
 6. The process of claim 4 wherein the reaction conditionsinclude temperature ranging from about 185° to about 200° C. and timeranging from about 0.25 to about 2 hours.
 7. The process of claim 1wherein the acid catalyst is naphthylaminium hydrochloride.
 8. A processfor preparing a 1,3,5-tris(4'-hydroxyaryl)benzene compound of formula(I): ##STR8## wherein R is hydroxy, R¹ is hydrogen, C₁ -C₁₂ alkyl, C₃-C₆ cycloalkyl, phenyl, halogen, nitro, or alkyl or aromatic sulfonyl, xis an integer from 1 to 4, and when x is greater than 1, each R' thereofcan be the same or different, said process comprising: (i) reacting asubstituted 4-hydroxyacetophenone compound of formula (II): ##STR9##wherein R, R¹ and x are as defined above, at about 80°-160° C. for about2-24 hours, with a substituted or unsubstituted aniline derivative, saidsubstituents being on the aromatic ring and being selected from thegroup consisting of a C₁ -C₆ alkyl, C₁ -C₆ alkoxy and halo groups,wherein said compound II is present in at least three molar ratioquantities, and wherein said aniline derivative is present in a molarratio range of about 1:1 to about 10:1 with respect to compound II,whereby a substituted 4-hydroxyacetophenone-anil compound of formula(III) ##STR10## wherein R, R¹ and x are as defined above, is formed, and(ii) reacting said compound of formula (III) with an acid catalyst atabout 150°-220° C. for about 0.25 to about 4 hours, with water beingcontinuously removed from the reaction of step (ii), wherein saidcompound III is kept substantially anhydrous prior to said reaction ofstep (ii), wherein said acid catalyst is present in a molar ratio rangeof about 1:4 to about 1:100 with respect to compound III, and whereinsaid catalyst is a salt of aniline or naphthylamine with said aniline ornaphthylamine being substituted or unsubstituted in its aromatic ring,said substituents being selected from the group consisting of a C₁ -C₆alkyl, C₁ -C₆ alkoxy and halo groups.
 9. The process of claim 8 whereinsaid aniline derivative in step (i) is aniline and said acid catalyst instep (ii) is anilinium hydrochloride.
 10. The process of claim 8 whereinx is 1 and R¹ is hydrogen.
 11. The process of claim 9 wherein x is 1 andR¹ is hydrogen.
 12. The process of claim 8 wherein step (i) is withoutisolation of compound of formula (III).
 13. The process of claim 8wherein said reaction of step (i) is performed at about 1500 to about180° C. for about 2-17 hours, and said reaction of step (ii) isperformed at temperature ranging from about 185° to about 200° C. andtime ranging from about 0.5 to about 2 hours.
 14. The process of claim 8wherein the mole ratio of said aniline derivative to the compound offormula (II) in step (i) is about 1:1 to about 2:1 and the mole ratio ofsaid acid catalyst to the compound of formula (III) in step (ii) isabout 1:12.5 to about 1:25.
 15. The process of claim 14 wherein step (i)includes adding a solvent.
 16. The process of claim 8 wherein step (i)includes adding a solvent.
 17. The process of claim 15 or claim 16wherein said solvent is a non-polar organic solvent.
 18. The process ofclaim 8 wherein step (i) includes isolating compound of formula (III).19. A process for preparing a 1,3,5-tris(4'-hydroxyaryl)benzene compoundof formula (I) ##STR11## wherein R is hydroxy, R¹ is hydrogen, C₁ -C₁₂alkyl, C₃ -C₆ cycloalkyl, phenyl, halogen, nitro, or alkyl or aromaticsulfonyl, x is an integer from 1 to 4, and when x is greater than 1,each R¹ thereof can be the same or different, said process comprisingreacting a substituted 4-hydroxyacetophenone compound of formula (II)##STR12## wherein R, R¹ and x are as defined above, wherein saidcompound II is present in at least three molar quantities, with asubstituted or unsubstituted aniline derivative, said substituents beingon the aromatic ring and being selected from the group consisting of aC₁ -C₆ alkyl, C₁ -C₆ alkoxy and halo groups, said aniline being presentin a molar ratio range of about 1:1 to about 10:1 with respect tocompound II, at about 150° to about 220° C, for about 0.5 to about 8hours, in the presence of an acid catalyst at about 150°-220° C. forabout 0.25 to about 4 hours, wherein said acid catalyst is present in amolar ratio range of about 1:4 to about 1:100 with respect to compoundIII, and wherein said catalyst is a salt of aniline or naphthylaminewith said aniline or naphthylamine being substituted or unsubstituted inits aromatic ring, said substituents being selected from the groupconsisting of a C₁ -C₆ alkyl, C₁ -C₆ alkoxy and halo groups.
 20. Theprocess of claim 19 wherein said acid catalyst is aniliniumhydrochloride.
 21. The process of claim 19 wherein x is 1, and R¹ ishydrogen.
 22. The process of claim 19 wherein the reaction conditionsinclude temperatures ranging from about 185° to about 220° C. and timesranging from about 0.5 to about 6 hours.
 23. The process of claim 20wherein the mole ratio of aniline derivative to the compound of theformula (II) is about 1:1 to about 2:1 and the mole ratio of aniliniumhydrochloride to the compound of the formula (II) is about 1:12.5 to1:25.
 24. The process of claim 19 further comprising adding a solvent.